Estimating the Severity Profile of Enterovirus A71 Infections in Children: A Bayesian Synthesis Framework

Enterovirus A71 (EV-A71) is responsible for the majority of severe cases of hand, foot, and mouth disease, but little evidence is available on the severity profile of EV-A71 infections. We formulated a hierarchical Bayesian model that synthesized data on diseases/events associated with EV-A71 and EV-A71 antibody responses to infection among unvaccinated children from large clinical trials of EV-A71 vaccination, which were conducted in Jiangsu and Beijing during 2012 and 2013, to reconstruct the severity profile in a unified framework. On average, 15.1% of the children aged 6-35 months were infected by EV-A71 during 1-year follow-up in a mild epidemic season. We estimated that 9.7%, 2.2%, and 0.6% of children infected with EV-A71 were diagnosed with EV-A71-associated diseases, were hospitalized, and showed severe complications, respectively. We estimated on average 1 death per 10,000 EV-A71 infections for children aged 6-35 months. Approximately 70% of children had ≥4-fold rises in antibody titers after infection. Most EV-A71 infections in young children are mild, and overall 2.2% of the infected patients were hospitalized in the 2 trials. There remain several uncertainties about the immune response after infection and the duration of immunity against EV-A71 reinfection.